3. Definitions
Shutterstock ID: 286407365
Fat Deposition in
Liver
The
macrovesicular
steatosis that
occupies at least
5% of the
hepatocytes
Simple Steatosis
Presence of fat in
the liver with or
without the
presence of lobular
inflammation on
histology
Non-alcoholic Steatohepatitis or NASH
Steatosis and inflammation are associated with the
presence of one of the following 3 additional features
on liver histology:
Ballooning of hepatocytes
Mallory hyaline bodies
Fibrosis
Duseja J, et al. J Clin Exp Hepatol. 2015;5(1):51-68.
5. Non-alcoholic fatty liver disease
NAFLD is probably the most common liver
disease in many countries affecting 10%
to 24% of the general population.
There is a direct correlation between body
mass index (BMI) and prevalence and
severity of NAFLD.
Annals of hepatology 2002; 1(1): January-March: 12-19
12. Prevalence in Asian
Countries
Prevalence (%) of NAFLD in different Asian
countries are as follows1:
Prevalence of NASH in patients with biopsy-proven
NAFLD is 63.5%3
China 15%-40%
India 30%
Japan 25%-30%
Korea 27%
Affects around a quarter of the Asian adult population.1
NAFLD
epidemic in
Asia1,2
Obesity
Metabolic
syndrome
Urbanisation
Sedentary
lifestyle
Western diet
1. Fan JG, et al. J Hepatol. 2017;67(4):862-873.
2. Pati GK, et al. Euroasian J Hepatogastroenterol. 2016;6(2):154-162.
3. Younossi ZM, et al. Hepatology. 2016;64(1):73-84.
NAFLD, non-alcoholic fatty liver
disease; NASH, non-alcoholic
steatohepatitis.
18. Obesity - a major ethiologic factor
in NAFLD
The prevalence of fatty liver in the general population is
about 23%
The prevalence among alcoholics reaches 46%, among
the obese - 95%, and among alcoholics who are
overweight - 76%
Consequently, fatty liver is caused by obesity in a
greater extent than by alcohol
1. Drapkina OM, Smirin VI, VT Ivashkin Nonalcoholic fatty liver disease - a modernapproach to the problem. Attending Doctor. 2010. Т. 5. # 5. pg.
57–61.
2. Drapkina OM, Smirin VI, VT Ivashkin Pathogenesis, treatment and epidemiology ofNAFLD - what's new? Epidemiology of NAFLD in Russia.
RMJ. 2011; 28: 1717-1722
21. Gut microbiota :Pathogenesis of
NAFLD
(1)Increased production and absorption of gut short-
chain fatty acids
(2)Altered dietary choline metabolism by the microbiota
(3)Altered bile acid pools by the microbiota
(4)Increased delivery of microbiota derived ethanol to
liver
(5)Gut permeability alterations and release of endotoxin
(6)Interaction between specific diet and microbiota
August
22
22. LEAN NASH
• The pathophysiology may be quite different.
• Genetic predispositions, fructose- and cholesterol-
rich diet, visceral adiposity and dyslipidaemia.
• Risk for metabolic disturbances, cardiovascular
morbidity or overall mortality.
• Secondary causes to be ruled out
• The effectiveness of exercise and
pharmacotherapy-not known.
• Weight loss is expected to help in visceral obesity
• Further investigation is needed- mechanistic
pathogenesis, risk assessment, natural history and
therapeutic approach
August
23
23. Proposed risk stratification for patients with NAFLD
Rinella, M. E. & Sanyal, A. J. (2016) Management of NAFLD: a stage-based approach
Nat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2016.3
ALT
24.
25. Noninvasive Imaging of
Steatosis
Abdominal ultrasound1,2
First-line investigation for patients with suspected hepatic
steatosis
Qualitative assessment of fatty infiltration of liver
Presence of >33% fat on liver biopsy, optimal for detection
of steatosis by ultrasound
Characteristic sonographic features3: Attenuation
of image quickly within 4 to 5 cm of depth, making
deeper structures, difficult to decipher
• Echogenic diffusely but particularly important to
note brightness within the first 2 to 3 cm of depth
• Liver is uniformly heterogeneous
• Thick subcutaneous depth (>2 cm)
• Liver fills entire field with no edges visible
(viewed as helpful but not necessary for
diagnosis)
29. Simple noninvasive tests of
fibrosis
• NAFLD fibrosis score: age,
hyperglycaemia, body mass
index, platelet count, albumin,
AST/ALT ratio
• BARD score: body mass index,
AST/ALT ratio, type 2 diabetes
mellitus
• FIB-4 score: age, AST, ALT
30. NAFLD - a chronic inflammatory
process
There is a correlation between levels of CRP
and IL-6 and the degree of inflammation
and fibrosis in NAFLD
Wieckowska A et al. Am J Gastroenterol 2008;103:1372–1379
31. Serum Biomarkers
• Biomarkers can be used in differentiating simple
steatosis from NASH1
• But, biomarkers are still under evaluation1
• Potential biomarkers: cytokeratin-18 and terminal
peptide of procollagen III1
NASH, non-alcoholic
steatohepatitis.
1. Dyson JK, et al. Frontline Gastroenterol. 2014;5(3):211-218.
2. J Hepatol. 2016;64(6):1388-1402.
Stock photo ID: 615791984
Serum biomarkers can be an acceptable alternative for diagnosis of steatosis
when imaging modalities are not available.2
35. ~500 kcal restriction daily equates to weight reduction of 0.45Kg
per week.
Diets restricted in carbohydrate typically provide a rapid initial
weight loss.
Adherence to the diet is more important than which diet is chosen.
A high-quality diet— i.e., enriched in fruits, vegetables, whole
grains, lean poultry, and fish—should be encouraged to provide
the maximum overall health benefit.
DIET---
36. PHYSICAL ACTIVITY-
60–90 min of daily activity (At least 30 min.) Gradual increases in physical activity
should be encouraged to enhance adherence and avoid injury.
Some high-risk patients should undergo formal cardiovascular evaluation before
initiating an exercise program.
Physical activity could be formal exercise such as jogging, swimming, or tennis or
routine activities, such as gardening, walking, and housecleaning.
37. Role of LSM in NAFLD
LSM IS THE CORNERSTONE OF NAFLD MANAGEMENT
EXERCISE AND
CALORIC
RESTRICTION
INDUCING
WEIGHT LOSS
ARE NEEDED TO
IMPROVE NAFLD
38. Statins and NAFLD
Safety: ↑ AST / ALT in 1-3% of patients
There are no convincing data on the relationship
between ↑ AST / ALT and histologically verified liver
damage against statins
Atorvastatin (80 mg) reduced the AST / ALT,
and possibly reduced steatosis[Gomez-Dominguez, 2006;
Kiyici, 2003]
Pravastatin (80 mg) reduced ALT [Lewis et al. 2007]
Possible mechanisms
- Reduction of TNF-alpha, IL-6, CRP,
- Reduced delivery of FFA to the liver, the effect on insulin
through adiponectin
39. Statins for NAFLD: molecular mechanisms
Argo C.K., Loria P., Statins in liver disease: a molehill,
an iceberg, or neither? // Hepatology. 2008 Aug;48(2):662–9.
• Effect on the metabolism of the
gene sonic hedgehog (sHh) -
progression of fibrosis
and reparative mechanisms
• Inhibition of sHh reduces weight
gain from dietary habits
• sHh: effects on stellate cells
and possible involvement in the
pathogenesis of Cirrhosis sonic hedgehog
40. A Fasting triglyceride value of <150 mg/dL is recommended. A
weight reduction of >10% is necessary to lower fasting
triglycerides.
A fibrate (gemfibrozil or fenofibrate) is the drug of choice to
lower fasting triglycerides and typically achieve a 35–50%
reduction.
Other drugs that lower triglycerides include statins, nicotinic
acid, and high doses of omega-3 fatty acids.
TRIGLYCERIDES
41. For rise in HDL cholesterol, weight reduction is an important
strategy.
Nicotinic acid is the only currently available drug with
predictable HDL cholesterol-raising properties.
Statins, fibrates, and bile acid sequestrants have modest effects
(5–10%), and there is no effect on HDL cholesterol with
ezetimibe or omega-3 fatty acids.
HDL Cholesterol
42. • OCA
• Lubiprostone
• DMR- Procedure
• DPP4
• Saroglitazar
• Elafibrinor
• Empagliflozin
• Fecal Microbiota Transplantation
• Current and Potential future drugs
Newer approaches
44. New therapeutic strategies in
nonalcoholic fatty liver disease: a focus
on promising drugs for nonalcoholic
steatohepatitis
New therapeutic strategies in nonalcoholic fatty liver disease: a focus
on promising drugs for nonalcoholic steatohepatitis
Natalia Pydyn 2020
48. Effects of Interventions in NAFLD
Weight
Loss
Insulin
Resista
nce
Liver
Enzymes
Inflam
matio
n
Fibrosis
Lifestyle
interventions
Yes Yes Yes Yes Unproven
Vitamin E No No Yes Yes No
Pioglitazone Weight
gain
Yes Yes Yes Might be
beneficial
Ursodeoxychol
ic acid
No Yes Yes Yes Might be
beneficial
Metformin Yes Yes No No No
Gitto S, et al. Gastroenterol Res Pract. 2015;2015:732870.
